ALIPHATIC AND ALICYCLIC DIOLS INDUCE MELANOGENESIS IN CULTURED-CELLS AND GUINEA-PIG SKIN

We have found that several aliphatic and alicyclic diols induce melano genesis in cultured S91 mouse melanoma cells and normal human epiderma l melanocytes (NHEM). In addition, these compounds induce melanogenesi s when applied to guinea pig skin, with transfer of melanin to keratin ocytes and formation of ''supranuclear caps,'' as occurs in naturally pigmented skin. The relative order of potency of some of these diols i n NHEM is 5-norbornene-2,2-dimethanol > 3,3-dimethyl-1,2-butanediol > cis-1,2-cyclopentanediol > 2,3-dimethyl-2,3-butanediol > 1,2-propanedi ol. Following treatment with these diols or 3-isobutyl-1-methylxanthin e, melanin and tyrosinase activity are increased within S91 cells and NHEM; however, for cultured NHEM, the largest increases of melanin and tyrosinase occur in an extracellular particulate fraction, shown by e lectron microscopy to consist almost entirely of stage III and IV mela nosomes. These results indicate that cultured NHEM treated with diols export melanosomes in a fashion that is commensurate with natural mela nogenic processes. In contrast, S91 mouse melanoma cells exhibit aberr ant melanosomal trafficking, in accordance with the known defect in my osin-V mediated melanosomal transport, Both S91 cells and NHEM exhibit morphologic changes and growth arrest indicative of differentiation f ollowing treatment with diols. The diols described in this report are candidates for use as cosmeceutical tanning agents.